Mechanisms of group transfer reactions and their catalysis will be studied in enzymic and nonenzymic systems and mechanisms for the conversion of chemical energy into work will be examined with the calcium-transporting ATPase of sarcoplasmic reticulum. This subject is important in the control and function of healthy and diseased muscle. The role of exact fixation and entropy loss in enzyme catalysis will be probed with partial and complete substrates for Coenzyme A transferase and by examining small changes in the size of substituents that are remote from the reacting groups of substrates. Rate and equilibrium constants for formation and breaking of hydrogen bonds in aqueous solution will be examined. The mechanism of calcium internalization and the internal calcium binding site of the calcium ATPase will be characterized. Phosphoryl transfer will be examined by a search for general base catalysis and for catalysis of the cleavage of phosphorylated pyridines by alkaline phosphatase. Acyl cyanides will be examined as substrates for chymotrypsin in an attempt to estimate the role of proton transfer to the leaving group in catalysis; concerted proton transfer to the leaving cyanide is not possible. The mechanism of proton transfer between electronegative atoms will be examined by determining Bronsted plots and isotope effects for general acid and general base catalysis of ester aminolysis involving diffusion-controlled proton transfer. Reactions of acyl halides will be examined to evaluate the importance of acylium ion intermediates and the possibility of a bimolecular substitution mechanism. The mechanism of proton removal from carbon will be studied using the sulfonium ion as activating group to determine if there are changes in transition state structure with changing reactant structure; these compounds are expected to have a small intrinsic barrier for proton transfer that may make such changes more readily detectible.